Introduction
Rearrangements of the histone-lysine N-methyltransferase 2A (KMT2A -r; formerly mixed lineage leukemia; MLL ) gene on chromosome 11q23 are the hallmark of infantile acute lymphoblastic leukemia (ALL) and confer particularly poor prognosis.1 KMT2A rearrangements induce transcriptional and epigenetic alterations that confer early blocks in B-cell differentiation resulting in an immature B-cell immunophenotype, increased lineage plasticity, and resistance to therapy.2–4 Among the >130 partner genes previously identified, the most common KMT2A -r is the t(4;11)(q21;q23) that results in the KMT2A/AFF1 fusion gene and is associated with B-cell acute lymphoblastic leukemia (B-ALL) presenting with a pro-B cell immunophenotype.5KMT2A -r leukemias have been associated with lineage switching from lymphoid to myeloid immunophenotype at relapse, demonstrating increased lineage plasticity.6–9
This report details the case of an infant with KMT2A -r ALL who experienced multiple immunophenotype switches during therapy. Her disease was refractory to standard therapy but ultimately went into remission with a combination of myeloid- and lymphoid-directed therapy.